The objectives of the Protein Localization, Identification and Folding (PLIF) Core is to connect investigators to imaging techniques, particularly confocal and electron microscopy, highly specialized mass spectrometry and the new area of protein folding as related to digestive diseases. This Core has evolved since the origin of the GI Center in 1986, when it was a morphology core, to one encompassing newer and more sophisticated techniques of protein identification and localization. In the last funding period that began in 2010, the Core has been known as the Protein Identification and Localization Core. The new proposed PLIF Core has added a more robust and state-of-the-art mass spectrometry facility that is part of an institutionally funded Protein Folding Diseases Initiative at the University of Michigan. Given that multiple GI diseases, including hepatitis, inflammatory bowel diseases and pancreatitis, involve abnormalities of protein folding resulting in endoplasmic reticulum and other organelle stress, this adds another new dimension to the Core and takes advantage of significant institutional investments. The specific aims of the PLIF Core are: (1) Provide state of the art protein localization and identification facilities. Core programs include: Imaging, Proteomics and Protein Folding Diseases Initiative resources; (2) Ensure delivery of high quality services and products and provide technical oversight of all PLIF services; and (3) Train and educate members, associate members and pilot feasibility recipients in the application and use of protein identification techniques for the study of digestive and liver diseases. The most popular Core service is access to well-maintained confocal microscopes and software for image processing and 3-D image reconstruction. Other broadly used services include the evaluation of fine structure by electron microscopy and the identification of proteins and their post-translational modifications by mass spectrometry both of which are carried out by expert Core personnel. Other added aspects are an Aperio AT2 scanner and software for image analysis of stained tissue sections, and a laser capture microdissection system. The Core is directed by Drs. Asma Nusrat and Bishr Omary, two experienced and established investigators with extensive expertise in the services provided by the Core. During the current cycle of the grant, the Protein Identification and Localization Core services were used by 76% of Center members; and supported 116 publications with primary PLIF Core usage, of which 48 were collaborative publications among two or more Center members. We anticipate a similar fraction of Center members, including pilot awardees, to make use of the expanded PLIF Core. We also expect to effectively partner with the other Cores of the Center and with other NIH-supported centers, and to continue to provide state-of-the-art and efficient services and promote collaborations to synergistically advance GI research and discoveries.